Astrocytes: a central element in neurological diseases

Abstract

The neurone-centred view of the past disregarded or downplayed the role of astroglia as a primary component in the pathogenesis of neurological diseases. As this concept is changing, so is also the perceived role of astrocytes in the healthy and diseased brain and spinal cord. We have started to unravel the different signalling mechanisms that trigger specific molecular, morphological and functional changes in reactive astrocytes that are critical for repairing tissue and maintaining function in CNS pathologies, such as neurotrauma, stroke, or neurodegenerative diseases. An increasing body of evidence shows that the effects of astrogliosis on the neural tissue and its functions are not uniform or stereotypic, but vary in a context-specific manner from astrogliosis being an adaptive beneficial response under some circumstances to a maladaptive and deleterious process in another context. There is a growing support for the concept of astrocytopathies in which the disruption of normal astrocyte functions, astrodegeneration or dysfunctional/maladaptive astrogliosis are the primary cause or the main factor in neurological dysfunction and disease. This review describes the multiple roles of astrocytes in the healthy CNS, discusses the diversity of astroglial responses in neurological disorders and argues that targeting astrocytes may represent an effective therapeutic strategy for Alexander disease, neurotrauma, stroke, epilepsy and Alzheimer’s disease as well as other neurodegenerative diseases.

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Acknowledgments

The authors thank Roy Pekny for critical comments on the manuscript and acknowledge support from the Swedish Medical Research Council (Project 11548 and 20116), Deutsche Forschungsgemeinschaft (STE 552/3), AFA Research Foundation, ALF Göteborg (Project 11392 and 142821), Sten A. Olsson Foundation for Research and Culture, Söderberg Foundations, Hjärnfonden, Hagströmer’s Foundation Millennium, the Swedish Stroke Foundation, the Swedish Society for Medical Research, the Free Mason Foundation, Amlöv’s Foundation, E. Jacobson’s Donation Fund, NanoNet COST Action, (BM1002), the EU FP 7 Programs EduGlia (237956), NeuroGLIA (202167), EuroEPINOMICS and TargetBraIn (279017). AV was supported, in part, by the Grant (agreement from August 27 2013 No. 02.B.49.21.0003) between The Ministry of Education and Science of the Russian Federation and Lobachevsky State University of Nizhny Novgorod, by the Ministry of education of Russian Federation, unique identity number of the project is RFMEFI57814X0079, and by the grant of the Russian Scientific Foundation No. 14-15-00633. VP’s work is supported by the National Institutes of Health (HD078678). The concept of this review was conceived at the conference and training school Astrocyte Intermediate Filaments (Nanofilaments) and Astrocyte Function in Health and Disease, held at the University of Gothenburg, Sweden, in 2014, supported by NanoNet COST Action (BM1002), and the Swedish Medical Research Council, with the authors of this review as speakers.

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Pekny, M., Pekna, M., Messing, A. et al. Astrocytes: a central element in neurological diseases. Acta Neuropathol 131, 323–345 (2016). https://doi.org/10.1007/s00401-015-1513-1

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Keywords

  • Astrocytes
  • Astroglial cells
  • Reactive astrogliosis
  • Reactive gliosis
  • Astrocytopathies
  • Neurotrauma
  • Stroke
  • Epilepsy
  • Alzheimer’s disease
  • Alexander disease
  • Huntington disease
  • Neurological diseases